Babesiosis, caused by infection with intra-erythrocytic parasites of the genus Babesia, is one of the most common infections of free living animals worldwide and is gaining increasing interest as an emerging zoonosis (a disease communicable from animals to humans). Babesia are transmitted by their tick vectors during the taking of a blood meal from the vertebrate host. Babesiosis has long been recognized as an economically important disease of cattle, but only in the last 30 years has Babesia been recognized as an important pathogen in man. Human babesiosis is caused by one of several Babesial species that have distinct geographical distributions based on the presence of competent hosts. In North America, babesiosis is caused predominantly by Babesia microti, a rodent borne parasite, and also occasionally by two newly recognized species, WA1 and MO-1. In Europe, human babesiosis is considerably rarer but more lethal, and is caused by the bovine pathogen B. divergens. The spectrum of disease is broad, ranging from an apparently silent infection to a fulminant, malaria-like disease which can be fatal. When present, symptoms typically are non-specific (fever, headache and myalgia). A number of factors have contributed to the “emergence” of human babesiosis, including increased awareness among physicians, changing ecology, and an increased population of immuno-compromised individuals susceptible to infection. Since 1980, over 500 cases of human infections have been reported.
Parasites that live in red blood cells (RBCs, erythrocytes) have rather ingenious ways of gaining entry to these cells. The best studied is Plasmodium spp, the etiological agent of malaria. Like Plasmodium, Babesia merozoites enter RBCs using an active invasion process that is mediated by multiple receptor-ligand interactions. The various ‘steps’ in the invasion process in both Plasmodium and Babesia have been illustrated using light and electron microscopy and microcinematography. They are identical in both apicomplexans, except for the fact that soon after entry of the Babesia merozoite, the parasitophorous vacuolar membrane disappears. The invasion, growth and maturation of both Plasmodium and Babesia within the human erythrocyte is accompanied by both morphological and biochemical changes in the RBC plasma membrane, which can be attributed to the activity of specific, parasite derived factors. Parasite derived proteases are of particular importance as they play a pivotal role in both the entry and the exit of the parasite by processing both parasite adhesins and host erythrocyte proteins. Serine protease inhibitors can block invasion by Plasmodium and Babesia divergens. It is therefore hypothesized that serine proteases function during B. divergens merozoite invasion, much like they do in P. falciparum, in two potential ways: the proteolysis of RBC surface and skeletal proteins and the processing of parasite proteins. Recently the “sheddase” that is responsible for the proteolytic shedding of P. falciparum surface proteins during invasion was identified as a membrane bound subtilisin-like protease called PfSUB2.